Cell transformation by papovaviruses requires the expression of several early viral gene products. Our laboratory is currently investigating the mechanism by which papillomaviruses (human and bovine) and polyomavirus perturb cell growth control and participate in tumorigenesis. The main research focus will be on human papillomaviruses (HPV). Although the role of HPV in benign human tumors (warts) is well established, it is only recently that an association between HPV and cervical cancer has been defined. More than 25 types of HPV exist (by DNA hybridization). Only a few of these HPVs are associated with cervical cancer, however. For example, type 16 appears to be found in various stages of cervical dysplasia (or "flat warts") as well as in carcinioma-in-situ and invasive carcinoma. Type 18 HPV is found only in invasive cervical carcinoma. The biological role of these viral genomes in tumor cells is unknown, but the ability of related bovine papillomaviruses (BPV) to transform cells in vitro suggests that HPV may have a role in either initiating or maintaining the transformed state. Our interest is to define the types of HPV in cervical squamous cell carcinomas, to determine whether their DNA is transcribed into mRNA, and hopefully to detect virus-specific proteins in the tumor cells. We will also attempt to transform cells in vitro with HPV DNA. Selected, formal studies with BPV will be performed for com-comparison of HPV and BPV transforming properties. Related to our attempts to transform cells with HPV is an effort to transform epithelial cells in vitro. Our laboratory has an interest in defining the progressive stages of carcinogenesis and, as part of this study, to establish an in vitro system for the transformation of epithelial cells. We have decided to focus on human and murine epidermal cells since much is known about the murine model for the induction of squamous cell carcinioma and since these cells can be propagated in vitro. Culture conditions for human epidermal cells are also well estalished. Our initial attempt will include transfecting murine epidermal cells with BPV and polyoma DNA and human epidermal cells with HPV-16 and HPV-18 DNA.